title: Histopathological features of patients with chronic pancreatitis due to mutations in the PRSS1 gene: evaluation of BRAF and KRAS2 mutations.
abstract: OBJECTIVE
  Hereditary pancreatitis (HP) is a rare cause of chronic pancreatitis (CP; 1%) and more than 25 mutations in the PRSS1 gene have been detected. HP patients with the p.R122H mutation have a 35% lifetime risk of developing pancreatic cancer, but the oncogenetic process remains unknown. We have investigated the histopathological features and frequency of BRAF and KRAS2 mutations in 2 patients with PRSS1 mutations (p.A121T, p.R122H) and patients with CP (n = 11).
  
  
  METHODS
  Pancreatic tissue was stained with hematoxylin-eosin and examined by light microscopy. Mutational analysis of the BRAF (exon 5, 11) and KRAS2 (exon 1) genes was performed using PCR and direct DNA sequencing.
  
  
  RESULTS
  Histopathological features revealed similar results in both patients, pancreata showed strong fibrosis and ducts with signs of distortion, irregular size and noticeable dilatations. We identified one BRAF mutation (p.V600E) in the p.R122H patient and two KRAS2 (p.G12D; p.G12C) mutations in CP controls.
  
  
  CONCLUSIONS
  Our results sustain the knowledge about the clinical phenotype of patients with PRSS1 mutations who have a high risk of pancreatic cancer. Whether the histopathological picture or the BRAF mutation is specific for patients with PRSS1 mutations or plays a specific role in the tumorigenesis of patients with HP needs to be further evaluated.
authors.affiliation: Department of Medicine I, St. Josef Hospital, Ruhr University School of Medicine, Bochum, Germany. peter.felderbauer@rub.de
authors.forename: Peter
authors.initials: P
authors.lastname: Felderbauer
authors.forename: Ingo
authors.initials: I
authors.lastname: Stricker
authors.forename: Jurgen
authors.initials: J
authors.lastname: Schnekenburger
authors.forename: Kerem
authors.initials: K
authors.lastname: Bulut
authors.forename: Ansgar M
authors.initials: AM
authors.lastname: Chromik
authors.forename: Orlin
authors.initials: O
authors.lastname: Belyaev
authors.forename: Christophe A
authors.initials: CA
authors.lastname: Muller
authors.forename: Waldemar
authors.initials: W
authors.lastname: Uhl
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010179:Pancreas / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D014357:Trypsin; D014362:Trypsinogen / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D014362:Trypsinogen; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C489303:PRSS1 protein, human; D014357:Trypsin; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins